In vitro comparison of major memory support dietary supplements for their effectiveness in reduction/inhibition of beta amyloid protein fibrils ...
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OPEN In vitro comparison of major
memory‑support dietary
supplements for their effectiveness
in reduction/inhibition
of beta‑amyloid protein fibrils
and tau protein tangles: key
primary targets for memory loss
Alan D. Snow1*, Joel A. Cummings1, Rudolph E. Tanzi2 & Thomas Lake1
Memory loss is primarily caused by the accumulation of both brain plaques [(consisting of beta-
amyloid protein (Aβ) 1–42)] and neurofibrillary tangles (consisting of paired helical and straight
filaments containing tau protein). Neuroinflammation is the third key and important factor that
leads to accelerated memory loss and eventual dementia. Brain plaques, tangles and inflammation
is the trilogy mainly responsible for causing memory loss that has now been documented for over
20 years in the scientific literature. The present investigation used in vitro quantitative methods
to directly compare the ability of major memory-support dietary supplements to reduce pre-
formed Aβ 1–42 fibrils (21 supplements tested) and tau protein paired helical/straight filaments
(13 supplements tested)—two of the three most important targets for memory loss. Additionally,
18 different manufacturers of cat’s claw (Uncaria tomentosa) were directly compared for their
ability to inhibit/reduce Aβ 1–42 fibrils and/or tau paired helical/straight filaments based on recent
findings that PTI-00703 cat’s claw is a specific and potent inhibitor/reducer of all three targets -brain
plaques, tangles and inflammation (Snow et al. in Sci Rep 9:561, 2019). In the present investigation
quantitative Thioflavin T fluorometry was used on a comparative weight-to-weight basis at increasing
concentrations with ingredients tested from the actual capsules the consumer ingests. Major memory-
support dietary supplements were directly compared for their ability to inhibit and disaggregate/
reduce both Aβ 1–42 fibrils and/or tau paired helical/straight filaments. Dietary supplements touted
to enhance memory comparatively tested included Prevagen, FOCUSfactor, PROCERA AVH, Alpha
Brain, NAD+OVIM, BRAIN JUICE, Cebria, EXCELEROL, NOOCUBE, US Doctor’s Clinical Brain Power
ADVANCED, healthycell pro, LUMONOL, Brain Awake, BRAIN ARMOR, brainMD (BRAIN & MEMORY
POWER BOOST), Brain Support, Clarity (BRAIN HEALTH FORMULA), brainMD (NEUROVITE PLUS),
neuriva (Original and Plus) and percepta. This is the first paper to actually comparatively test these
memory-support supplements for their ability to reduce Aβ fibrils and tau protein tangles. Percepta
(PTI-00703 cat’s claw and a specific oolong tea extract) was determined to be the most effective and
potent memory support dietary supplement to disaggregate/disrupt Aβ 1–42 fibrils (range of 25–89%)
and tau paired helical/straight filaments (range of 26–86%) at all 3–4 doses tested in comparison to
other major memory-support dietary supplements tested. This was at least more than double (> 50%)
for percepta reducing Aβ 1–42 fibrils and in comparison to the other 20 memory-support dietary
supplements tested. The ranking order for memory-support supplement effects based on reducing
1
Cognitive Clarity Inc., Edmonds, WA 98026, USA. 2Genetics and Aging Research Unit, Department of Neurology,
Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. *email: dralansnow@
cognitiveclarityinc.com
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Aβ 1–42 fibrils (Aβ 1–42: memory-support supplement at 1:0.1 weight-to-weight in a 3-day study)
was percepta (69.6% reduction) >>> Alpha Brain (34.9% reduction) = US Doctor’s Clinical Brain Power
ADVANCED (32.4%) = BRAIN JUICE (30.1%) = neuriva Plus (27%) = neuriva Original (27%) > NEUROVITE
PLUS (22.9%) = NOOCUBE (19.9%) = EXCELEROL (17.3%) = healthycell pro (17.2%) > Prevagen
(12.9%) > PROCERA AVH (6.5%) = FOCUSfactor (5.5%) > Cebria (0%) = Brain Awake (0%) = Brain
Support (0%) = brainMD (BRAIN & MEMORY POWER BOOST) (0%) = NAD+OVIM (0%) = BRAIN ARMOR
(0%) = LUMONOL (0%). The ranking order for memory support supplement effects on reducing
tau paired helical/straight filaments (tau:memory supplement at 1:1 weight-to-weight at 3 days)
was percepta (85.7% reduction) >>> neuriva Plus (57.9%) >> BRAIN JUICE (41.9%) = EXCELEROL
(41.0%) = neuriva Original (38.4%) = US Doctor’s Clinical Brain Power ADVANCED (38.3%) = healthycell
pro (37.6%) >> Alpha Brain (27.9%) >> NOOCUBE (17.6%) >> FOCUSfactor (8.7%) > Cebria
(3.6%) = PROCERA AVH (0%) = Prevagen (0%). Congo red staining, Thioflavin S fluorescence, circular
dichroism (CD) spectroscopy and electron microscopy confirmed the positive results observed
with the supplement percepta. CD spectroscopy demonstrated that percepta caused a marked
inhibition of beta-sheet secondary folding of tau protein into paired helical filaments. PTI-00703
cat’s claw (main ingredient in percepta) was also identified as the most potent cat’s claw bark powder
(Uncaria tomentosa) to reduce and inhibit Aβ 1–42 fibrils and tau tangles in comparison to 17 other
manufacturers of cat’s claw extracts. Although there are thousands of brain memory-support dietary
supplements in the marketplace today, none of them have been directly compared and analyzed
for their ability to reduce and/or inhibit two major targets of memory loss i.e. Aβ 1–42 fibrils and tau
paired helical/straight filaments (major constituents of brain plaques and tangles). In our comparison
studies, we show that percepta has the most potent ability to disaggregate/reduce Aβ 1–42 fibrils and
tau protein paired helical/straight filaments as demonstrated by a variety of methods most likely due
to the specific polyphenol content in PTI-00703 cat’s claw (i.e. polyphenols and proanthocyanidins) as
we have previously shown (Snow et al. in Sci Rep 9:561, 2019). Memory-support dietary supplements
tested that also contained polyphenols and/or cat’s claw in their product demonstrated some Aβ
fibril and tau protein tangle reducing activity, but were much less effective than percepta. Percepta’s
main ingredient, PTI-00703 cat’s claw, has previously been shown to reduce brain amyloid plaques
and Aβ 1–42/40 insoluble/soluble levels in brain (in plaque-producing transgenic mice) with marked
concurrent memory improvements (shown by Morris water maze testing) (Snow et al. in Sci Rep 9:561,
2019). The present investigation further confirms that percepta is one of the best dietary supplements
that causes a marked reduction and inhibition of Aβ fibrils and tau tangle filaments -two important
major targets for memory-support. In addition, PTI-00703 cat’s claw was the most effective cat’s claw
(Uncaria tomentosa) ingredient for reducing /disaggregating and inhibiting Aβ 1–42 fibrils and tau
protein paired helical/straight filaments in comparison to 17 other manufacturers of cat’s claw extracts
tested.
Memory loss has been shown to be primarily caused by the accumulation of three major factors: (1) the accu-
mulation and persistence of Swedish meatball looking-like amyloid plaques in brain between neurons consisting
mainly of a 40–42 amino acid peptide called beta-amyloid protein or Aβ1,2, (2) the accumulation of dried-
spaghetti-like strands inside dying neurons consisting primarily of a microtubule-associated protein called tau
protein3; and (3) n euroinflammation4. The trilogy of memory loss leading to dementia and Alzheimer’s disease
(AD) in nearly 100% of the cases is therefore the accumulation and persistence in brain of Plaques, Tangles and
Inflammation (referred to as PTI)5.
As one normally ages, Aβ amyloid plaque accumulation occurs as early as 20 years old and increases
progressively6. The build-up of tau protein in neurofibrillary tangles also increases during normal aging and is
believed to occur shortly after brain plaque accumulation7. Normal brain aging in healthy individuals therefore
involves the brain build-up of both plaques and tangles. When the accumulation of brain plaques and tangles
begins to be excessive, memory loss and cognitive decline worsen, and can first appear clinically as mild cogni-
tive impairment (MCI). Increased brain persistence of plaques and tangles associated with neuroinflammation
is the tipping point of marked neuronal loss that can eventually lead to the diagnosis of AD (based on memory
testing, the ruling out of other diseases and using brain PET imaging techniques in live patients to confirm the
diagnosis)8,9. In AD, there is an accumulation of thousands, to hundreds of thousands of plaques and tangles
in specific brain regions including hippocampus and cortex. If plaques and tangles are the matches that light
the brain on fire, then neuroinflammation ignites the neuron-killing forest fi re10–13. Thus, the trilogy of brain
plaques, tangles and inflammation is postulated to lead to a marked potential and rapid decline in memory
and cognition in the aging population. Although there may be other potential causes of memory loss including
oxidative stress14, reduced blood flow15, reduced synaptic integrity16,17, reduced plasticity processes18,19, the most
documented studies that lead to memory loss and eventual dementia is the accumulation of brain plaques (i.e.
Aβ fibrils), neurofibrillary tangles (i.e. tau protein filaments) and neuroinflammation as observed in AD -the
most common cause of memory loss problems among older adults20.
In our previous study, Snow et al.5 identified an extract from the woody vine, Uncaria tomentosa (i.e. cat’s
claw) that markedly reduced and inhibited both Aβ amyloid plaques and tau protein tangles. A specific cat’s claw
from bark powder of a woody vine growing deep in the Peruvian Amazon rain forest referred to as PTI-00703
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cat’s claw was used. This led to the development of a unique dietary supplement for memory-support (called
percepta) that basically consisted of just two bioactive ingredients, PTI-00703 cat’s claw and a specific oolong
tea extract. 10 years of research studies with 8 different institutions led to a landmark paper by Snow et al.5 in
which newly discovered polyphenols (i.e. specific proanthocyanidins or epicatechin-dimers) in PTI-00703 cat’s
claw entered the brain within two minutes of being in the blood. In plaque-producing double mutation TASD-
41 transgenic mice, the main proanthocyanidin B2 in PTI-00703 cat’s claw reduced brain plaque load (in older
animals) by 57% and improved short-term memory (assessed by Morris water maze testing) by 58% following a
short 3-month treatment. Neuroinflammation (both astrocytosis and microgliosis) was also markedly decreased
by 69–80% in the brains of these animals following 3-months of t reatment5. Percepta was developed to be the
first dietary and memory-support supplement to specifically target brain plaques and tangles.
In the present studies, quantitative Thioflavin T fl uorometry21–23 determined the effects of different major
memory-support dietary supplements to disaggregate/dissolve Aβ 1–42 fibrils (major constituent in brain amy-
loid plaques) and/or tau protein containing paired helical/straight filaments (major constituent in brain neurofi-
brillary tangles). Other methods to confirm effects of the most effective memory-supplement identified to reduce
Aβ 1–42 fibrils and tau protein tangles (i.e. percepta) included Congo red staining (i.e. red/green birefringence
under polarized light)24, Thioflavin S fluorescence25, and electron microscopy (to visualize plaque amyloid fibrils
or tangle paired helical filaments)26. Circular dichroism (CD) spectroscopy also determined its effects to reduce
β-sheet secondary folding5.
In the present investigation, we compared major memory-support dietary supplements to reduce and/or
inhibit brain Aβ 1–42 fibrils and/or tau protein paired helical/straight filaments. Comparisons were made on a
direct weight-to-weight (wt/wt) basis on the actual capsule ingredients used for oral consumption by consum-
ers. Both disruption/disaggregation of pre-formed Aβ 1–42 fibrils (21 memory-support products tested) and
pre-formed tau filament tangles (13 memory-support products tested) were specifically analyzed. Comparisons
were made between Prevagen, FOCUSfactor, PROCERA AVH, Alpha Brain (contains cat’s claw), N AD+OVIM
(contains cat’s claw), BRAIN JUICE, Cebria, EXCELEROL, NOOCUBE (contains cat’s claw), US Doctor’s Clinical
Brain Power ADVANCED, healthycell pro , LUMINOL, Brain Awake, BRAIN ARMOR, brainMD (BRAIN &
MEMORY POWER BOOST), Brain Support, Clarity (BRAIN HEALTH FORMULA), brainMD (NEUROVITE
PLUS), neuriva (neuriva Original and neuriva Plus) and percepta. Percepta was found by far to be the best dietary
supplement that was a potent disaggregator/disruptor of Aβ 1–42 fibrils and tau tangles in comparison to the
other major memory-support dietary supplements.
Additionally, we compared 18 different manufacturers of cat’s claw (Uncaria tomentosa) for their ability to
reduce Aβ 1–42 fibrils, inhibit Aβ 1–40 fibril formation, and/or reduce tau tangles. PTI-00703 cat’s claw (the main
ingredient in Percepta) demonstrated the most robust activity for Aβ fibril and tau tangle reduction/inhibition
compared to all the other cat’s claw extracts tested from different manufacturers. Cat’s claw (Uncaria tomentosa)
is a known and potent reducer of neuroinflammation due to its ability to reduce the inflammatory cytokines
TNF-alpha and interleukin-127–31. This study demonstrated that one of the best dietary supplements targeting Aβ
fibrils (major constituent of brain plaques) and tau paired helical/straight filament (major constituent in brian
neurofibrillary tangles) was percepta.
Results
Percepta is the most effective reducer of brain Aβ 1–42 plaque fibrils in comparison to 20 other
major memory‑support dietary supplements. Thioflavin T fluorometry quantitated, differentiated
and compared the effects of different major memory-support dietary supplements on Aβ 1–42 fibril reduction
and disaggregation (Table 1). Aβ 1–42 protein is the major protein found in amyloid plaques in the aging brain
and in AD32. In the first set of studies, 21 different memory-support dietary supplements were compared directly
to each other on a weight-to-weight (wt/wt) basis for their ability to disaggregate and reduce pre-formed Aβ 1–42
fibrils. Brain supplements directly compared in different sets of studies were percepta, Prevagen, FOCUSfactor,
PROCERA AVH, Alpha Brain (contains cat’s claw), N AD+OVIM (contains cat’s claw), BRAIN JUICE, Cebria,
EXCELEROL, NOOCUBE (contains cat’s claw), US Doctor’s Clinical Brain Power ADVANCED, healthycell pro,
LUMONOL, Brain Awake, BRAIN ARMOR, brainMD (BRAIN & MEMORY POWER BOOST), Brain Support,
Clarity (BRAIN HEALTH FORMULA), brainMD (NEUROVITE PLUS), and neuriva (neuriva Original and
neuriva Plus) (Table 1).
As demonstrated in Fig. 1A, Aβ 1–42 was first incubated at 37 °C to observe instant amyloid fibril formation
by Thioflavin T fluorometry at day 0 (3,050 fluorescent units; black bar on left). This was confirmed by positive
Congo red staining (i.e. red-green birefringence as viewed under polarized light) (Fig. 5, top left)5 and positive
Thioflavin S fluorescence (Fig. 5, middle left)5. Aβ 1–42 also demonstrated amyloid fibrils at day 0, as shown by
negative stain electron microscopy (Fig. 5, lower left)5. In a first study (Fig. 1A), percepta was identified as the
most potent disrupter of Aβ 1–42 fibrils in comparison to ten (10) other major memory-support dietary sup-
plements on a wt/wt basis and in a dose-dependent manner (Aβ 1–42:dietary supplement ratios tested of 1:0.01;
1:0.1 and 1:1). Increasing doses of percepta demonstrated a marked dose-dependent disaggregation/disruption
of pre-formed Aβ 1–42 fibrils (Fig. 1A,B). Aβ 1–42 amyloid plaque fibril reduction at the pre-determined clinical
dose of percepta (i.e. 1:0.1 wt/wt)5 caused a significant (p < 0.001) 69.6% disaggregation/reduction of pre-formed
Aβ 1–42 fibrils (Fig. 1B). Most of the other memory-support dietary supplements tested had much less effects
on reduction of Aβ 1–42 fibrils at the 1:0.1 wt/wt dose (Table 1).
As shown in Fig. 2A, in a second comparison study, Aβ 1–42 first incubated at 37 °C demonstrated instant
amyloid fibril formation by Thioflavin T fluorometry at day O (i.e. 2654 fluorescence units; black bar on left).
Percepta was again identified as the most potent disrupter of Aβ 1–42 amyloid plaque fibrils in comparison to
seven (7) other memory-support dietary supplements on a wt/wt basis and in a dose-dependent manner (Aβ
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Dietary supplement Major ingredients/daily % Reduction of Aβ 1–42 % Reductio of Tau Tangles Reported mechanism of
product name/company serving size (total) fibrils (1:0.1 wt/wt) (1:1 wt/wt) Solubility issues action/claims
Targets/reduces brain
PTI-00703 cat’s claw;
Percepta plaques and tangles;
oolong tea extract (2 cap- 69.6 85.7 No
(Cognitive Clarity Inc.) improves memory, focus and
sules/750–775 mg)
concentration
l-tyrosine; l-theanine; PS;
Alpha Brain cat’s claw; GPC; bacopin; Improves memory, focus and
34.9 27.9 No
(Onnit Labs) vinpocetine (2 cap- processing speed
sules/1315 mg)
Vitamin B6; B12; ginkgo
Supports memory and
US Doctor’s Clinical Brain biloba; green tea; choline;
mental sharpness; promotes
Power ADVANCED huperzine A; vinpocetine; 32.4 38.3 No
healthy circulation in the
(US Doctors Clinical) acetyl-l-carnitine (2 cap-
brain
sules/1086 mg)
Vitamin C; B6; B12; choline;
green tea; acetyl-l-carnitine;
BRAIN JUICE Focus; Clarity; Memory;
acai berry; blueberry; 30.1 41.9 No; used liquid
(Brain Juice) Mood
l-theanine (1 bottle/2.5 fl.
oz.)
Supports focus, memory,
Neuriva Plus Coffee fruit extract; PS
27.0 57.0 No learning, accuracy and
(Schiff Vitamins) (1 capsule; ~ 302 mg)
concentration
Supports focus, memory,
Neuriva Original Coffee fruit extract; PS
27.0 38.4 No learning, accuracy and
(Schiff Vitamins) (1 capsule; 200 mg)
concentration
Vitamins; calcium;
magnesium; zinc; choline;
brainMD Multiple nutrients for sharp
hesperidin; blueberries; 22.9 NT No
(NEUROVITE PLUS) minds and healthy bodies
strawberries; broccoli; spin-
ach; PS; coenzyme Q10;
Alpha-GPC; cat’s claw; oat
straw; huperzine A; bacopin;
NOOCUBE Improves your cognitive
l-theanine; l-tyrosine; vin- 19.9 17.6 No
(Wolfsen Berg Ltd) functioning
pocetine; pterostilbene
(2 capsules/997.5 mg)
Vitamin B12; niacin;
Huperzine A; vinpocetine;
EXCELEROL acetyl-l carnitine; Bacopin;
Supports memory, concen-
(Accelerated Intelligence green tea; ginkgo biloba; 17.3 41.0 No
tration and alertness
Inc.) peppermint; PS; l-tyrosine;
white tea; black tea (2 cap-
sules/ ~ 325 mg)
Vitamins; Minerals;
Bilberry; Rosemary;
Pycnogenol; Lutein; cat’s
Healthycell pro claw; turmeric; milk thistle; Supports energy and mental
17.2 37.6 No
(HealthyCell) Korean ginseng; coenzyme focus
Q10; N-acetyl-cysteine; gotu
kola; l-theanine; green tea;
resveratrol; pterostilbene;
Prevagen Apoaequorin (jelly fish pro- Small dispersible particles;
12.9 0 Improves memory
(Quincy Biosciences) tein) (1 capsule/10 mg) dissolvable
Acetyl-l-carnitine; vin-
PROCERA AVH Supports brain health and
pocetine; huperzine A (3 6.5 0 No
(Procera Health) cognitive function
capsules/1515 mg)
Various vitamins; bacopin;
DHA; bilberry fruit extract;
FOCUSfactor Improves memory, concen-
grape seed extract; 5.5 8.7 No
(Synergy CHC Corp.) tration and focus
huperzine A; (4 tab-
lets/2768 mg)
Vitamins; green tea; baco-
Improves focus and memory;
Clarity pin; bilberry; grape seed
5.1 NT No higher mental processing;
(Neovicta) extract; PS; cinnamon bark;
boost creativity
N-acetyl-tyrosine
Vitamin B6; B12; folic acid;
Cebria l-theanine; green tea; amino Significantly improves
0.0 3.6 No
(Cebria LLC) acids memory & recall
(1 capsule/459 mg)
Vitamin B6; B12; MCT oil;
Promotes focus and mental
bacopin; l-theanine; rose-
Brain Awake clarity; support retention of
mary; lemon balm; black 0.0 NT No
(Irwin Naturals) information; enhance perfor-
pepper; tea extract
mance on cognitive tasks
(3 soft gels/2218 mg)
Continued
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Dietary supplement Major ingredients/daily % Reduction of Aβ 1–42 % Reductio of Tau Tangles Reported mechanism of
product name/company serving size (total) fibrils (1:0.1 wt/wt) (1:1 wt/wt) Solubility issues action/claims
Vitamin B6; B12; alpha
GPC; lion’s mane; bacopin;
Brain Support tyrosine; ginkgo biloba; Supports memory and
0.0 NT No
(1 Body) PS; l-theanine; taurine; cognition
huperzine A;
(3 capsules/2,152 mg)
BrainMD (BRAIN & MEM- PS; acetyl-cysteine; ginkgo
Supports healthy brain and
ORY POWER BOOST) biloba; vinpocetine; huper- 0.0 NT No
memory performance
(BrainMD Health) zine A;
Magnesium; thiamine;
NAD+OVIM bacopin; cat’s claw; NAD + ; Supports brain function,
0.0 NT No
(Innovative Medicine LLC) co-enzyme Q10 focus and concentration
(2 capsules/911 mg)
Omega-3′s; DHA; EPA;
BRAIN ARMOR
MCT oil 0.0 NT No For strong brains
(Brain Armor Inc)
(2 capsules; 2028 mg)
N-acetyl l-tyrosine; l-thea-
LUMONOL Helps improve focus; pre-
nine; caffeine (2 capsules; 0.0 NT No
(Advanse Nutraceuticals) workout energy booster
600 mg)
Table 1. Comparison of 21 memory-support supplements for reduction of Aβ 1–42 fibril and/or tau tangles.
Major ingredients and reported mechanism of action/claims are also compared for each product DHA
docosahexaenoic acid, NT not tested, EPA eicosapentaenoic acid, MCT medium chain triglycerides, NAD+
nicotinamide adenine dinucleotide, PS phosphatidylserine.
1–42:dietary supplement ratios tested of 1:0.001, 1:0.01; 1:0.1 and 1:1) (Fig. 2A). Aβ 1–42 amyloid plaque fibril
reduction at the pre-determined clinical dose of percepta (i.e. 1:0.1 wt/wt)5 caused a significant (p < 0.001) 43.9%
disaggregation/reduction of pre-formed Aβ 1–42 fibrils (Fig. 2B). None of the other brain supplements were even
close to reducing Aβ 1–42 fibrils in comparison to percepta on a wt/wt basis (Table 1).
As shown in Fig. 3A and B, in a third comparison study, Aβ 1–42 first incubated at 37 °C demonstrated instant
amyloid fibril formation by Thioflavin T fluorometry at day O (i.e. 2800 fluorescence units; black bar on left).
Percepta was again identified as the most potent disrupter of Aβ 1–42 fibrils in comparison to neuriva Original,
neuriva Plus and Prevagen on a wt/wt basis and in a dose-dependent manner (Aβ 1–42:dietary supplement ratios
tested of 1:0.001, 1:0.01; 1:0.1 and 1:1). Aβ 1–42 fibril reduction at the pre-determined clinical dose of percepta
(i.e. 1:0.1 wt/wt)5 caused a significant (p < 0.001) 45.3% disaggregation/reduction of pre-formed fibrils (Fig. 3B).
Neuriva Original and neuriva Plus has some effects most likely due to the coffee cherry polyphenols in the dietary
supplement but were not as effective on disaggregating/dissolving Aβ 1–42 fibrils on a wt/wt basis in comparison
to percepta. Prevagen again demonstrated no effects on disaggregating/dissolving Aβ 1–42 fibrils on a wt/wt basis.
As shown in Fig. 4A and B, in a fourth comparison study, Aβ 1–42 first incubated at 37 °C demonstrated
instant amyloid fibril formation by Thioflavin T fluorometry at day 0 (i.e. 2,450 fluorescent units; black bar on
left). Percepta was again identified as the most potent disrupter of Aβ 1–42 fibrils in comparison to N AD+OVIM
on a wt/wt basis and in a dose-dependent manner (Aβ 1–42:dietary supplement ratios tested of 1:0.001, 1:0.01;
1:0,1 and 1:1). Aβ 1–42 fibril reduction at the pre-determined clinical dose of percepta (i.e. 1:0.1 wt/wt)5 caused a
significant (p < 0.001) 48.4% disaggregation/reduction of pre-formed fibrils (Fig. 4B). NAD+OVIM (even though
it contains cat’s claw as an ingredient) was not effective at all in disaggregating/dissolving Aβ 1–42 fibrils on a
wt/wt basis. Prevagen again demonstrated no effects on disaggregating/dissolving Aβ 1–42 fibrils on a wt/wt
basis (Table 1).
The ranking order (criteria described in “Methods”) for memory-support supplement effects from the four
studies on reducing Aβ 1–42 fibrils (Aβ 1–42: dietary supplement at 1:0.1 wt/wt) was percepta (69.6% reduc-
tion) >>> Alpha Brain (34.9%) = US Doctor’s Clinical Brain Power ADVANCED (32.4%) = BRAIN JUICE
(30.1%) = neuriva Plus (27.0%) = neuriva Original (27.0%) > brainMD (NEUROVITE PLUS) (22.9%) = NOO-
CUBE (19.9%) = EXCELEROL (17.3%) = healthycell pro (17.2%) > Prevagen (12.9%) > PROCERA AVH
(6.5%) = FOCUSfactor (5.5%) > Cebria (0%) = Brain Awake (0%) = Brain Support (0%) = brainMD (BRAIN &
MEMORY POWER BOOST) (0%) = NAD+OVIM (0%) = BRAIN ARMOR (0%) = LUMONOL (0%) (Table 1).
Figure 5 demonstrates the effects of percepta at a 1:1 wt/wt (Aβ 1–42:percepta) on reduction/dissolution of
Aβ 1–42 fibrils by three different independent methods following 1 day of treatment. Aβ 1–42 fibrils show instant
red-green birefringence indicative of amyloid fibrils when stained with Congo red (i.e. red/green birefringence as
viewed under polarized light; Fig. 5A). A marked decrease in Congo red straining (i.e. red/green birefringence)
was observed in the presence of percepta indicating a marked reduction of Aβ 1–42 fibrils (Fig. 5B). Thioflavin S
fluorescence also demonstrated the presence of massive Aβ 1–42 fibrils as shown by positive green fluorescence
(Fig. 5C). A marked decrease and near elimination in Thioflavin S fluorescence following incubation with per-
cepta further demonstrated a marked reduction in Aβ 1–42 fibrils (Fig. 5D). Negative stain electron microscopy
demonstrated massive accumulation of Aβ 1–42 fibrils as viewed at 30,000 magnification (Fig. 5E). A marked
decrease /dissolution of Aβ 1–42 fibrils was observed at the electron microscopic level in the presence of percepta
(Fig. 5F), confirming the reductions observed with Congo red staining and Thioflavin S fluorescence.
Percepta was the most effective reducer of tau protein paired helical/straight filaments in
comparison to 12 other major memory‑support dietary supplements. In two sets of tau tangle
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Figure 1. Percepta is the most potent disrupter of Aβ 1–42 fibrils in comparison to ten (10) other top-selling
brain supplements. (A) Percepta (containing PTI-00703 cat’s claw and a specific oolong tea extract) was
compared to Prevagen, FOCUSfactor, PROCERA AVH, Alpha Brain (contains cat’s claw), BRAIN JUICE,
Cebria, EXCELEROL, NOOCUBE (contains cat’s claw), US Doctor’s Clinical Brain Power ADVANCED and
healthycell pro (contains cat’s claw) for disruption of Aβ 1–42 fibrils. Percepta was the most potent disrupter /
disaggregator of pre-formed Aβ 1–42 fibrils than any of the other 10 brain supplements tested (on a wt/wt basis)
as quantitatively determined by Thioflavin T fluorometry. Aβ 1–42 formed fibrils instantly and showed 3,050
Thioflavin T fluorescent units (FU) due to immediate fibril formation (black bar). Increasing doses of percepta
(Aβ 1–42:percepta wt/wt ratios of 1:0.01; 1:0.1; and 1:1) demonstrated a marked dose-dependent disaggregation/
disruption of Aβ 1–42 fibrils. Amyloid plaque fibril reduction at 1:0.1 wt/wt is compared (blue line across
graph). *p < 0.05, **p < 0.01, ***p < 0.001, by Student’s t-test. Bars represent mean ± SEM. (B) Comparison of
percepta to 10 (ten) other top selling brain supplements in % disaggregation of preformed Aβ 1–42 fibrils.
Percepta had the most robust activity and reduced/disaggregated Aβ 1–42 fibrils in a dose-dependent manner
(light brown bars), better than other memory-support supplements including those that contained cat’s claw
(i.e. Alpha Brain, NOOCUBE and healthycell pro). At a Aβ:percepta wt:wt ratio of 1:0.1 (blue line across graph),
percepta disaggregated Aβ 1–42 fibrils by 69.6%, much better than any other brain supplement tested. *p < 0.05,
**p < 0.01, ***p < 0.001, by Student’s t-test. Bars represent mean ± SEM.
comparison studies, 13 different brain supplements were compared directly to each other on a wt/wt basis for
their ability to disaggregate and reduce pre-formed tau paired helical and straight filaments (major constituents
of neurofibrillary tangles). Testing was not determined for memory-support supplements that showed 0% effi-
cacy for Aβ 1–42 fibrils including Brain Awake, Brain Support, brainMD, N AD+OVIM, BRAIN ARMOR, and
LUMONOL. Memory-support supplements directly compared in a first set of studies were percepta, Prevagen,
FOCUSfactor, PROCERA AVH, Alpha Brain (contains cat’s claw), BRAIN JUICE, Cebria, EXCELEROL, NOO-
CUBE (contains cat’s claw), US Doctor’s Clinical Brain Power ADVANCED, healthycell pro (contains cat’s claw)
(Fig. 6C,D) and neuriva (neuriva Original and neuriva Plus) (Fig. 7A) (Table 1).
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Figure 2. Percepta was the most potent disrupter of Aβ 1–42 fibrils in comparison to seven (7) other top-selling
brain supplements on a wt/wt basis. (A) Percepta was compared to LUMONOL, Brain Awake, BRAIN ARMOR,
brainMD (BRAIN & MEMORY POWER BOOST), Brain Support, Clarity (BRAIN HEALTH FORMULA), and
brainMD (Neurovite Plus). Percepta, once again was the most potent disrupter /disaggregator of pre-formed Aβ
1–42 fibrils than any other brain supplement tested as determined quantitatively by Thioflavin T fluorometry.
Aβ 1–42 formed fibrils instantly and showed 2,654 Thioflavin T fluorescent units (FU)(black bar). Increasing
doses of percepta (Aβ 1–42:percepta wt/wt ratios of 1:0.001, 1:0.01; 1:0.1; and 1:1 were tested) demonstrated
a marked dose-dependent disaggregation/disruption of pre-formed Aβ 1–42 fibrils. All the other brain
supplements tested did not reduce Aβ 1–42 fibrils or only somewhat did so at the highest 1:1 wt/wt dose tested.
*p < 0.05, **p < 0.01, ***p < 0.001, by Student’s t-test. Bars represent mean ± SEM. (B) Comparison of percepta
to 10 (ten) other memory-support supplements in % disaggregation of preformed Aβ 1–42 fibrils. Percepta ,
by far, had the most robust activity and reduced/disaggregated Aβ 1–42 fibrils in a dose-dependent manner
(light brown bars). At a Aβ:percepta wt:wt ratio of 1:0.1 (blue line across graph), percepta disaggregated Aβ
1–42 fibrils by 4.29%, much better than any other brain supplement tested (see line across the graph). *p < 0.05,
**p < 0.01, ***p < 0.001, by Student’s t-test. Bars represent mean ± SEM.
Figure 6A and B demonstrated the formation of paired helical and straight filaments after 3 days of incuba-
tion with Tau-441 with the highly sulfated glycosaminoglycan, h eparin5,32–37. Paired helical filament formation
appeared identical to that seen in brain aging and AD5,32–37. These pre-formed tangles help compare the effects of
different memory-support supplements for disaggregation/reduction of pre-formed tau tangles using quantitative
Thioflavin T fluorometry as described below.
As shown in Fig. 6C, tangle formation was confirmed by Thioflavin T fluorometry at day 3 to reach 3,600
fluorescent units (black bar on left). Percepta was identified as the most potent disrupter of tau protein tangles in
comparison to the other ten (10) memory-support dietary supplements on a wt/wt basis and in a dose-dependent
manner (tau: dietary supplement ratios tested of 1:0.001, 1:0.01; 1:0.1 and 1:1) (Table 1). Increasing doses of
percepta demonstrated a significant dose-dependent disaggregation/disruption of pre-formed tau tangles at the
two highest doses tested (i.e. 1:0.01 and 1:1 wt/wt) (Fig. 6C, D). Tau tangle reduction at 1:0.1 wt/wt clinical dose
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Figure 3. Percepta outperformed neuriva (Schiff Vitamins) for disaggregation/disruption of pre-formed Aβ
1–42 fibrils. (A) Percepta was tested in comparison to neuriva (neuriva Original and neuriva Plus) and Prevagen
memory-support supplements on a wt/wt basis. Percepta was the most potent disrupter of Aβ 1–42 fibrils in
comparison to neuriva (neuriva Original and neuriva Plus) and Prevagen on a wt/wt basis as quantitatively
determined by Thioflavin T fluorometry. Aβ 1–42 fibrils demonstrate binding to Thioflavin T (indicator of fibril
formation) and 2800 fluorescence units. Percepta demonstrated the most robust disaggregation/dissolution of
pre-formed Aβ 1–42 fibrils. *p < 0.05, **p < 0.01, ***p < 0.001, by Student’s t-test. Bars represent mean ± SEM. (B)
Comparison (on a wt/wt basis) of percepta to neuriva (Original and Plus) and Prevagen for % disaggregation
of preformed Aβ 1–42 fibrils at 4 increasing dosages. Percepta had the most robust activity and reduced/
disaggregated Aβ 1–42 fibrils in a dose-dependent manner (light brown bars). At a Aβ:percepta wt:wt ratio of
1:0.1 (blue line across graph), percepta disaggregated Aβ 1–42 fibrils by 45.3%, whereas neuriva Original at that
dose only disaggregated Aβ 1–42 fibrils by 25.4%, neuriva Plus only disaggregated Aβ 1–42 fibrils by 30.2%, and
Prevagen did not work on amyloid plaque fibrils at all. *p < 0.05, **p < 0.01, ***p < 0.001, by Student’s t-test. Bars
represent mean ± SEM.
of percepta5 caused a significant (p < 0.001) 24.1% disaggregation/reduction of pre-formed fibrils (Fig. 6D), and
a significant (p < 0.001) 85.7% disaggregation at 1:1 wt/wt (Fig. 6D). All of the other memory-support dietary
supplements tested had little to no effects on disaggregation/reduction of pre-formed tangles, even those that
contained cat’s claw as part of their ingredients (i.e. Alpha Brain, NOOCUBE and healthycell pro all contain
cat’s claw) (Table 1).
As shown in Fig. 7A, in a separate study, tau protein induced by heparin demonstrated tangle formation as
shown by a marked increase in Thioflavin T fluorometry to 3120 fluorescent units (black bar on left). Percepta was
the most potent disrupter of tau tangles in comparison to neuriva Original, neuriva Plus and Prevagen on a wt/wt
basis and in a dose-dependent manner (tau: dietary supplement wt/wt ratios tested of 1:0.001, 1:0.01; 1:0.1 and
ercepta5 caused
1:1). Tau tangle disaggregation /dissolution at the pre-determined 1:0.1 wt/wt clinical dose of p
a significant (p < 0.001) 33.5% disaggregation/reduction of pre-formed tau tangles, and a significant (p < 0.001)
83.4% disaggregation/dissolution at a 1:1 wt/wt (Fig. 7B) (Table 1). Neuriva Original and neuriva Plus has some
effects but was more than 50% inferior to the reducing/disaggregation effects observed with percepta (Fig. 7B).
Again, Prevagen had no effect at all in reducing pre-formed tau tangles (Fig. 7B).
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Figure 4. Percepta outperformed NAD+OVIM for disaggregation/disruption of pre-formed Aβ 1–42 fibrils. (A)
Percepta was tested in comparison to NAD+OVIM and Prevagen supplements on a wt/wt basis. Percepta was
the most potent disrupter of Aβ 1–42 fibrils in comparison to N AD+ OVIM and Prevagen on a wt/wt basis as
quantitatively determined by Thioflavin T fluorometry. Aβ 1–42 fibrils demonstrate binding to Thioflavin T and
2,450 fluorescence units. Percepta demonstrated the most robust disaggregation/dissolution of pre-formed Aβ
1–42 fibrils. *p < 0.05, **p < 0.01, ***p < 0.001, by Student’s t-test. Bars represent mean ± SEM. (B) Comparison
(on a wt/wt basis) of Percepta to NAD+ OVIM and Prevagen for % disaggregation of preformed Aβ 1–42 fibrils
at four increasing dosages. Percepta had the most robust activity and reduced/disaggregated amyloid plaque
fibrils in a dose-dependent manner (light brown bars). At a Aβ:percepta wt:wt ratio of 1:0.1 (blue line across
graph), percepta disaggregated Aβ 1–42 fibrils by 48.4%, whereas N AD+ OVIM (that also contains cat’s claw) at
that dose only disaggregated Aβ 1–42 fibrils by 13.3%, and Prevagen did not work on amyloid plaque fibrils at
all. *p < 0.05, **p < 0.01, ***p < 0.001, by Student’s t-test. Bars represent mean ± SEM.
The ranking order for memory support supplement effects on reducing tau paired helical/straight fila-
ments (tau: dietary supplement at 1:1 wt/wt at 3 days) was percepta (85.7% reduction) >>> neuriva Plus
(57.9%) >> BRAIN JUICE (41.9%) = EXCELEROL (41.0%) = neuriva Original (38.4%) = US Doctor’s Clini-
cal Brain Power ADVANCED (38.3%) = healthycell pro (37.6%) >> Alpha Brain (27.9%) >> NOOCUBE
(17.6%) >> FOCUSfactor (8.7%) > Cebria (3.6%) = PROCERA AVH (0%) = Prevagen (0%) (Table 1).
Percepta demonstrated a potent reduction/dissolution of Aβ 1–42 fibrils and tau tangles as
shown by electron microscopy and circular dichroism spectroscopy. Figure 8 demonstrates the
effectiveness of percepta on reduction of both Aβ 1–42 fibrils and tau protein tangles at a 1:1 wt/wt ratio fol-
lowing co-incubation for 3 days as shown by electron microscopy. In Fig. 8A, Aβ 1–42 amyloid plaque fibrils
(arrowheads) were visualized at high magnification (× 30,000). Aβ 1–42 amyloid fibrils in the presence of per-
cepta following 3 days of co-incubation demonstrated only amorphous non-fibrillar material remaining (arrow-
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Congo Red
Staining
A B
Fluorescence
C D
Electron
Microscopy
E F
A 1-42 only A 1-42 + percepta
Figure 5. Percepta dissolved/disaggregated Aβ 1–42 fibrils within 24 h as shown by Congo red staining,
Thioflavin S fluorescence and electron microscopy. (A) Aβ 1–42 fibrils show instant red-green birefringence
indicative of Aβ 1–42 amyloid fibrils when stained with Congo red. (B) A marked dissolution/reduction of
Congo red staining is observed in the presence of percepta. (C) Thioflavin S fluorescence showed massive
Aβ 1–42 amyloid fibrils by positive green fluorescence. (D) A marked decrease in Thioflavin S fluorescence
indicated that percepta dissolved Aβ 1–42 fibrils. (E) Negative stain electron microscopy demonstrated massive
accumulation of Aβ 1–42 fibrils. (F). A marked dissolution/reduction of Aβ 1–42 fibrils was observed in the
presence of percepta.
heads) (Fig. 8B). Tau protein tangles formed by tau-441 induced in the presence of heparin for 3 days can also be
visualized by electron microscopy (Fig. 8C). In the presence of percepta, a marked dissolution/disaggregation of
pre-formed tau protein tangles was observed (Fig. 8D). A time course study indicated that percepta dissolved/
disaggregated pre-formed tau tangles within 15 min of co-incubation (data not shown). Circular dichroism
spectroscopy revealed that percepta prevented the formation of β-sheet tau protein tangles (shifted to α-helix)
following co-incubation for 3 days (Fig. 8E). These studies confirm the reductive effects of percepta on both Aβ
1–42 fibrils and tau protein tangles.
PTI‑00703 Cat’s claw was the most effective reducer of Aβ 1–42 fibrils compared to 17 other
manufacturers of Cat’s claw. PTI-00703 cat’s claw (from Cognitive Clarity Inc. and main ingredient in
percepta) was also compared to 17 other cat’s claw sources for their ability to disrupt/dissolve pre-formed Aβ
1–42 amyloid plaque fibrils. In a first study, this included cat’s claw from Remedy’s Nutrition, elp essential, Pure
Mountain BOTANICALS, Best Naturals, PROGRESSIVE LABORATORIES, Peruvian Naturals, PHARMLINE,
GRUPO CENTROFLORA, STARWEST BOTANICALS, GoNutra, SWANSON, and RAINTREE FORMULAS.
PTI-00703 cat’s claw (exclusive to percepta) demonstrated the most robust dose-dependent disruption/disag-
gregation of pre-formed Aβ 1–42 amyloid plaque fibrils in comparison to the other cat’s claw extracts tested on
a wt/wt/basis (Fig. 9). At the clinical 1:0.1 wt/wt determined dose of Aβ 1–42:PTI-00703 cat’s c law5, there was a
51.4% reduction of Aβ 1–42 fibrils by PTI-00703 (Fig. 9; see blue line across graph). No other manufacturer of
cat’s claw demonstrated a similar effect at the 1:01 and 1:1 wt/wt doses like PTI-00703 cat’s claw for disruption of
pre-formed Aβ 1–42 fibrils (Fig. 9) (Table 2).
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Figure 6. Percepta is the most potent disrupter of tau protein tangles in comparison to ten (10) other major
brain supplements on a wt/wt basis. (A) Tau-441 induced by heparin forms paired helical filaments as shown
by electron microscopy. Scale bar = 50 nm. (B) Formation of massive aggregated tau protein paired helical
filaments following induction with heparin and shown by electron microscopy. Scale bar = 50 nm. (C) Percepta
was the most potent disrupter /disaggregator of pre-formed tau protein tangles than any other memory-
support supplement tested as shown quantitatively by Thioflavin T fluorometry. Tau protein-441 induced by
heparin forms paired helical filaments instantly and shows 3600 Thioflavin T fluorescent units (FU)(black
bar). Increasing doses of percepta (tau:percepta wt/wt ratios of 1:0.001, 1:0.01; 1:0.1; and 1:1) demonstrated a
marked dose-dependent disaggregation/disruption of pre-formed tau tangles. *p < 0.05, **p < 0.01, ***p < 0.001,
by Student’s t-test. Bars represent mean ± SEM. (D) Comparison of percepta to 10 (ten) other major memory-
support dietary supplements in % disaggregation of preformed Aβ 1–42 fibrils. Percepta had the most robust
activity and reduced/disaggregated tau tangles in a dose-dependent manner (light brown bars). Percepta
disaggregated tau protein tangles by 86.4% at a tau:percepta wt/wt of 1:1, and by 24.1% at a tau:percepta wt/wt
of 1:0.1, and much better than any other major memory-support dietary supplement tested including Prevagen,
FOCUSFactor and Alpha Brain. *p < 0.05, **p < 0.01, ***p < 0.001, by Student’s t-test. Bars represent mean ±
SEM.
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Figure 7. Percepta outperformed neuriva (Schiff Vitamins) for disaggregation /disruption of pre-formed
tau tangles. (A) Percepta was tested in direct comparison to neuriva (neuriva Original and neuriva Plus) and
Prevagen memory-support supplements on a wt/wt basis. Percepta was the most potent disrupter of tau tangles
in comparison to neuriva (neuriva Original and neuriva Plus) and Prevagen on a wt/wt basis as determined
quantitatively by Thioflavin T fluorometry. Tau protein tangles fibrils demonstrated binding to Thioflavin T
and 3,120 fluorescence units. Percepta demonstrated the most robust disaggregation/dissolution of pre-formed
tau tangles in a dose-dependent manner. *p < 0.05, **p < 0.01, ***p < 0.001, by Student’s t-test. Bars represent
mean ± SEM. (B) Comparison (on a wt/wt basis) of percepta to neuriva (Original and Plus) and Prevagen for
% disaggregation of pre-formed tau tangles at 4 increasing dosages. Percepta had the most robust activity and
reduced/disaggregated tau tangles in a dose-dependent manner (light brown bars). At a tau:percepta wt:wt ratio
of 1:0.1 (blue line across graph), percepta disaggregated tau tangles by 33.5%, whereas neuriva Original at that
dose only disaggregated tau tangles by 8.1%, neuriva Plus only disaggregated tau tangles by 10.4%, and Prevagen
did not work on reducing tau tangles at all. At a 1:1 wt/wt dose percepta reduced tau tangles by 85.7%, whereas
neuriva Original and neuriva Plus only reduced tau tangles by 38.4% and 57.4%, respectively, whereas Prevagen
had no effects at all. *p < 0.05, **p < 0.01, ***p < 0.001, by Student’s t-test. Bars represent mean ± SEM.
In a second study, PTI-00703 cat’s claw was compared to 5 other cat’s claw extracts for their ability to disag-
gregate/disrupt pre-formed Aβ 1–42 fibrils including those derived from HERBAL PLUS, NATURE’S HERBS,
Nature’s Way, NOW, and SOLARAY. From these cat’s claw extracts tested, PTI-00703 cat’s claw again demon-
strated the most robust activity in disrupting/disaggregation of pre-formed Aβ 1–42 fibrils in a dose-dependent
manner, and in comparison to the other cat’s claw extracts tested (Fig. 10A,B). At a 1:0.1 wt/wt PTI-00703 cat’s
claw demonstrated a 48.4% disaggregation/dissolution of pre-formed Aβ 1–42 fibrils, whereas the other cat’s
claw extracts demonstrated much less activity (less than 20%) at that same dose (Fig. 10B).
The ranking order for cat’s claw (Uncaria tomentosa) effects on reducing Aβ 1–42 plaque fibrils (Aβ
1–42:cat’s claw extract at 1:0.1 wt/wt) was PTI-00703 cat’s claw (51.2% reduction) >> GRUPO CENTRO-
FLORA (39.3%) = GoNutra (34.4%) > NOW (27.7%) = STARWEST BOTANICALS (25.6%) = SWANSON
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Figure 8. Disruption of Aβ 1–42 fibrils and tau protein tangles by percepta as shown by negative stain
electron microscopy. (A) Aβ 1–42 fibrils (arrowheads) at 3 days as visualized by electron microscopy. × 30,000
magnification. (B) Aβ 1–42 fibrils in the presence of percepta following 3 days of co-incubation demonstrates
only amorphous non-fibrillar material remaining (arrowheads). (C) Tau protein tangles formed by tau-441
induced in the presence of heparin for 3 days. Bar = 200 nm. (D) Marked dissolution/disaggregation of pre-
formed tau protein tangles in the presence of percepta. Bar = 200 nm. (E) Percepta prevents formation of β-sheet
tau protein tangles (shifts to α-helix) within 72 h as determined by CD spectroscopy.
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Figure 9. Identification of PTI-00703 Cat’s claw (Uncaria tomentosa) as the most potent disrupter of Aβ 1–42
fibrils in comparison to other cat’s claw sources in the marketplace today. PTI-00703 Cat’s claw compared to
12 other cat’s claw sources for its ability to disrupt/dissolve pre-formed Aβ 1–42 fibrils. This included cat’s
claw from Remedy’s Nutrition, elp essential, Pure Mountain BOTANICALS, Best Naturals, PROGRESSIVE
LABORATORIES, Peruvian Naturals, PHARMLINE, GRUPO CENTROFLORA, STARWEST BOTANICALS,
GoNutra, SWANSON, and RAINTREE FORMULAS. PTI-00703 Cat’s claw demonstrated a dose-dependent
disruption/disaggregation of pre-formed Aβ 1–42 fibrils. At the Aβ 1–42:PTI-00703 cat’s claw dose of 1:0.1
wt/wt there was a 51.4% dissolution of plaque fibrils (blue line across graph). No other cat’s claw extract
demonstrated a similar effect at the 1:0.1 and 1:1 wt/wt doses like PTI-00703 Cat’s claw. *p < 0.05, **p < 0.01,
***p < 0.001, by Student’s t-test. Bars represent mean ± SEM.
(25.1%) = Peruvian Naturals (23.4%) = SWANSON (23.3%) = Best Naturals (21.5%) = PROGRESSIVE
LABORATORIES (19.9%) = RAINTREE FORMULAS (17.2%) = HERBAL PLUS (16.1%) = Remedy’s
Nutrition (15.9%) = Nature’s Way (15.4%) = NATURE’S HERBS (13.5%) = Pure Mountain BOTANICALS
(12.2%) > PHARMLINE (9.5%) = elp essential (8.0%) (Table 2). These studies also demonstrated that cat’s claw
is a potent inhibitor in reducing Aβ 1–42 fibrils but there are marked differences in efficacy depending on the
source of the cat’s claw with PTI-00703 being the most efficacious (Table 2).
PTI‑00703 Cat’s claw was the most potent inhibitor of beta‑amyloid 1–40 fibril formation com‑
pared to 5 other manufacturers tested. In another study, Thioflavin T fluorometry compared PTI-
00703 cat’s claw to other cat’s claw extracts (including HERBAL PLUS, NATURE’S HERBS, Nature’s Way, NOW,
and SOLARAY) for their ability to inhibit formation of Aβ 1–40 fibrils within a 3-day period. Aβ 1–40 peptide
formed amyloid fibrils detected by Thioflavin T fluorometry within 3 days (Fig. 10C,D). At the 1:0.1 wt/wt dose
of Aβ 1–40: PTI-00703 cat’s claw significantly (p < 0.001) inhibited Aβ 1–40 fibril formation by 52.3%, and at
the 1:1 wt/wt dose there was a significant (p < 0.001) 94.2% inhibition by PTI-00703 cat’s claw (Fig. 10D) . Cat’s
claw extracts obtained from HERBAL PLUS, NATURE’S HERBS, Nature’s Way, NOW, and SOLARAY) were far
inferior in inhibiting Aβ 1–40 fibril formation (Fig. 10D).
PTI‑00703 cat’s claw was the most potent reducer/disaggregator of tau protein tangles com‑
pared to cat’s claw extracts from 17 other manufacturers. Tau-441 protein was incubated with
heparin for 3 days to induce tau tangle paired helical filament f ormation5,35–37. Thirteen (13) different cat’s claw
extracts were then incubated for 3 days and compared on a wt/wt basis to determine their direct effects of reduc-
ing pre-formed tau tangles. As shown in Fig. 11A, PTI-00703 cat’s claw was the most potent disaggregator of tau
tangles in comparison to 12 other cat’s claw extracts tested, and did so in a dose-dependent manner (Table 2).
In this study, direct comparisons were made between PTI-00703 cat’s claw and cat’s claw extracts from Remedy’s
Nutrition, elp essential, Pure Mountain BOTANICALS, Best Naturals, PROGRESSIVE LABORATORIES, Peru-
vian Naturals, PHARMLINE, GRUPO CENTROFLORA, STARWEST BOTANICALS, GoNutra, SWANSON,
and RAINTREE FORMULAS. At the 1:0.1 wt/wt dose of tau protein: PTI-00703 cat’s claw significantly disaggre-
gated tau protein tangles by 34.3%. (Fig. 11A) Cat’s claw extract from GRUPO CENTROFLORA was the closest
to the robust activity demonstrated by PTI-00703 cat’s claw with only 21.3% disaggregation shown at the 1:0.1
wt/wt dose. (Fig. 11A). Comparisons of PTI-00703 cat’s claw in a separate study was also compared to 5 other
cat’s claw extracts including those obtained from HERBAL PLUS, NATURE’S HERBS, Nature’s Way, NOW, and
SOLARAY (Fig. 11B). Once again, PTI-00703 cat’s claw caused the most robust dose-dependent disaggregation
of pre-formed tau protein tangles than each of the other 5 cat’s claw extracts tested (Fig. 11B). At the 1:0.1 wt/
wt dose of Tau-441: PTI-00703 cat’s claw there was a significant (p < 0.001) 50.4% disaggregation of tau protein
tangles. At the 1:1 wt/wt dose PTI-00703 cat’s claw significantly (p < 0.001) disaggregation of tau protein tangles
by 92.3% (Table 2).
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Cat’s claw extract/product name/ % reduction of A13 1–42 % reduction of Tau
Company Major ingredients Fibrils (1:0.1 wt/wt) Tangles (1:1 wt/wt)
PTI-00703 cat’s claw (Cognitive Clarity
Cat’s claw (Uncaria tomentosa); 25 kg bags 51.2 90.1
Inc.)
GRUPO CENTROFLORA (Centroflora
Cat’s claw (Uncaria tomentosa) bark 39.3 86.6
Group)
Cat’s claw (Uncaria tomentosa) bark; bark
GoNutra (GoNutra) 34.4 61.2
powder in 1 lb bags
Cat’s claw (Uncaria tomentosa) bark;
NOW (Now Foods) 27.7 80.4
500 mg capsules
STARWEST BOTANICALS (Starwest Cat’s claw (Uncaria tomentosa) bark; bark
25.6 64.9
Botanicals Inc.) powder in 1
Cat’s claw (Uncaria tomentosa) bark;
SWANSON (Swanson Health Products) 25.1 45.2
500 mg capsules
Cat’s claw (Uncaria tomentosa) bark;
Peruvian Naturals (Peruvian Naturals) 23.4 25.1
500 mg capsules
Cat’s claw (Uncaria tomentosa) bark;
SOLARAY (Solaray) 23.3 62.0
500 mg capsules
Best Naturals Cat’s claw (Uncaria tomentosa) bark;
21.5 48.7
(Best Naturals) 500 mg capsules
PROGRESSIVE LABORATORIES (Pro- Cat’s claw (Uncaria tomentosa) bark;
19.9 33.5
gressive Laboratories) 500 mg capsules
RAINTREE FORMULAS (Raintree Cat’s claw (Uncaria tomentosa) bark;
17.2 51.9
Formulas) 500 mg capsules
Herbal Plus Cat’s claw (Uncaria tomentosa) bark;
16.1 45.1
(General Nutrition Corp.) 500 mg capsules
Cat’s claw (Uncaria tomentosa) bark
Remedy’s Nutrition (Remedy’s Nutrition) 15.9 60.2
1000 mg capsules
Nature’s Way Cat’s claw (Uncaria tomentosa) bark;
15.4 64.2
(Nature’s Way Products Inc) 335 mg capsules
Cat’s claw (Uncaria tomentosa) bark;
NATURE’S HERBS (Nature’s Herbs) 13.5 64.6
500 mg capsules
Pure Mountain BOTANICALS (Pure Cat’s claw (Uncaria tomentosa) bark;
12.2 51.0
Mountain Botanicals) 500 mg capsules
Cat’s claw (Uncaria tomentosa) bark
PHARMLINE (Pharmline Inc.) 9.5 60.3
500 mg capsules
Cat’s claw (Uncaria tomentosa) bark;
elp essential (Essential Products) 8.0 20.2
700 mg capsules
Table 2. Comparison of 18 cat’s claw extracts from different manufacturer’s for reduction of Aβ 1–42 fibril
and/or tau tangles. Major ingredient details are also compared for each product.
The ranking order for cat’s claw (Uncaria tomentosa) effects on reducing tau tangles (tau:cat’s claw extract
at 1:1 wt/wt) was PTI-00703 cat’s claw (90.1% reduction) = GRUPO CENTROFLORA (86.6% ) > NOW
(80.4%) >> STARWEST BOTANICALS (64.9%) = NATURE’S HERBS (64.6%) = Nature’s Way (64.2%) = SOLARAY
(62.0%) = GoNutra (61.2%) = PHARMLINE (60.3%) = Remedy’s Nutrition (60.2%) > RAINTREE FORMULAS
(51.9%) = Pure Mountain BOTANICALS (51.0%) = Best Naturals (48.7%) = SWANSON (45.2%) >> PROGRES-
SIVE LABORATORIES (33.5%) > Peruvian Naturals (25.1%) = elp essential (20.2%) (Table 2). These studies
demonstrated that cat’s claw is a potent inhibitor in reducing tau tangles but there are marked differences in
efficacy depending on the source (i.e. different manufacturers) of cat’s claw (Table 2).
At the tau:cat’s claw extract at 1:0.1 wt/wt, PTI-00703 cat’s claw reduced tau tangles by 30.2%, whereas GRUPO
CENTROFLORA reduced tangles by 15.3% (Fig. 11A) indicating that PTI-00703 cat’s claw is double the efficacy
of GRUPO CENTROFLORA cat’s claw at the more clinical dose of 1:0.1 wt/wt5.
Discussion
Causes of memory loss. Studies over the last 20 years now have determined that memory loss is primar-
ily caused by the accumulation in brain of three major factors, Plaques, Tangles and Inflammation (i.e. PTI)1,2.
Plaques look like giant Swedish-meatballs in the brain between neurons (i.e. nerve cells) and consist primarily of
a 42-amino acid peptide known as beta-amyloid protein or Aβ38,39. Brain tangles look liked dried-up spaghetti
inside neurons consisting of tau protein, a microtubule associated protein that normally functions in modulat-
ing the stability of axonal microtubules3. Both brain plaques and tangles are neurotoxic and cause neurons to
die40. Neuroinflammation is the third factor that accelerates and worsens the clinical manifestations of memory
loss13,41,42.
Aβ amyloid plaques in brain start accumulating in one’s early 20’s6,43,44. In Down’s syndrome (trisomy 21),
Aβ amyloid accumulation occurs inside neurons as soon as 1 day after birth26, and Down’s syndrome patients
end up having much of the same pathology as observed in human Alzheimer’s disease (AD) b rain26. Tau protein
tangles accumulate in brain shortly after Aβ plaque a ccumulation45,46. In seminal papers, organoids consisting
of human stem cells from patients with familial AD were placed on a Matrigel matrix (consisting of extracellular
Scientific Reports | (2021) 11:3001 | https://doi.org/10.1038/s41598-020-79275-1 15
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